Elevated expression of tumor necrosis factor‐α signaling molecules in colonic tumors of Zucker obese (fa/fa) rats
Bibliographic record
Abstract
Zucker obese rats are highly sensitive to colon cancer and possess a plethora of metabolic abnormalities including elevated levels of cytokine tumor necrosis factor-alpha (TNF-alpha). The main objective of this study was to determine if physiologically elevated TNF-alpha affects colonic tumor phenotype with regard to an altered TNF-alpha signaling pathway. Zucker obese (fa/fa, homozygous recessive for dysfunctional leptin receptors), Zucker lean (Fa/fa, Fa/Fa) and Sprague-Dawley (SD) rats were injected twice with azoxymethane (10 mg/kg) over 2 weeks. After 30 weeks, the animals were terminated and physiological and tumor parameters were assessed. Obese rats had notably higher body and organ weights as well as plasma TNF-alpha, insulin and leptin levels than lean or SD animals. A 100% tumor incidence and significantly higher tumor size, multiplicity and burden were found in obese rats compared to the lean group that had 47.8% tumor incidence. The SD group had the lowest tumor incidence (20.0%). Tumors from obese animals had higher protein levels of TNF-alpha, TNF-alpha-receptor-2 (TNFR2), nuclear transcription factor-kappaB (NF-kappaB) and IkappaB-kinasebeta (IKKbeta) compared to lean animals. In both obese and lean groups, expression levels of these proteins were higher in tumors than in surrounding, normal-appearing colonic mucosae. These findings support an important role for TNF-alpha signaling in tumorigenesis and demonstrate that tumors growing in an obese state had significantly different expression levels of TNFR2 and NF-kappaB, proteins known to play a critical role in growth and survival, than those growing in the lean state. It is concluded that the physiological state of the host intricately affects tumor phenotype.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".